Moderately diseased coronary arteries are frequently involved in acute thrombotic occlusion. Shear stress and its effect on platelet mediated thrombosis has been increasingly implicated in acute coronary syndromes. We believe that shear related platelet activation plays a pivotal role in coronary thrombosis and that factors which support thrombus formation are dependent on the shear environment and flow profiles. The aim of this proposal is to evaluate the platelet response to physiological levels and duration of shear stress, and to further define the roles of thrombin and platelet glycoprotein receptors Ib and IIb-IIIa in platelet mediated thrombosis. A canine model of coronary stenosis will be utilized. Shear stress associated with the stenosis will be calculated by the Finite Element Method. Platelet activation and secretion will be analyzed by quantitating the expression of platelet surface glycoproteins via fluorescent flow cytometry and serological parameters of platelet function. The goal of this project is to further our understanding of the complex process of thrombosis in an in vivo model of coronary occlusion and how flow profiles and hydrodynamic forces affect this process.